The overall goal of this program project is to develop effective strategies for treating patients with hematologic malignancies using radiolabeled monoclonal antibodies in conjunction with stem cell transplantation. Our studies have established the feasibility and anti-tumor activity of this approach and have led us to focus on several critical issues. The first is to fully establish The first is to fully establish the efficacy of our approach in extended Phase II trials and provide a basis for Phase III comparisons to conventional approaches. The second is to apply these approaches in patients not tolerant of current maximal dose therapies but who may benefit from a targeted therapy approach. The third is to improve the relative delivery of radiation to tumor compared to normal organs, an area critical for advancing this therapeutic modality. Thus, in Projects I and II, we will continue our Phase II trials, of radiolabeled antibody combined for patients with relapsed lymphoma or acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), and determine a basis for proceeding to definitive Phase III randomized trials. In elderly patients with lymphoma, we will investigate the feasibility and efficacy of administering single agent high-dose I-131- labeled anti-B-cell antibody and stem cell transplantation, and in elderly patients with advanced AML, we will investigate radiation delivered via I-131-anti-CD45 antibody combined with a low-dose, non-myeloablative regimen prior to matched related stem cell infusion. To improve delivery of radiation, in Project III we propose a novel approach a novel approach based on the rapid removal of circulating non-tumor bound radioisotope to decrease the radiation delivered to normal organs and improve the relative deliver of radiation to the tumor compared to those organs.